An investigation of the etiology and follow‐up findings in 35 children with overgrowth syndromes, including biallelic SUZ12 variant

Overgrowth‐intellectual disability (OGID) syndromes are clinically and genetically heterogeneous group of disorders. The aim of this study was to examine the molecular etiology and long‐term follow‐up findings of Turkish OGID cohort. Thirty‐five children with OGID were included in the study. Single gene sequencing, clinical exome analysis, chromosomal microarray analysis and whole exome sequencing were performed. Five pathogenic copy number variants were detected in the patients; three of them located on chromosome 5q35.2 (encompassing NSD1), others on 9q22.3 and 22q13.31. In 19 of 35 patients; we identified pathogenic variants in OGID genes associated with epigenetic regulation, NSD1 (n = 15), HIST1H1E (n = 1), SETD1B (n = 1), and SUZ12 (n = 2). The pathogenic variants in PIK3CA (n = 2), ABCC9 (n = 1), GPC4 (n = 2), FIBP (n = 1), and TMEM94 (n = 1) which had a role in other growth pathways were detected in seven patients. The diagnostic yield was 31/35(88%). Twelve pathogenic variants were novel. The common facial feature of the patients was prominent forehead. The patients with Sotos syndrome were observed to have milder intellectual disability than patients with other OGID syndromes. In conclusion, this study showed, for the first time, that biallelic variants of SUZ12 caused Imagawa‐Matsumoto syndrome, monoallelic variants in SETDIB resulted in OGID. Besides expanded the phenotypes of very rare OGID syndromes caused by FIBP and TMEM94.

• Publication year

  2023

• Venue

  American Journal of Medical Genetics. Part A

• Publication date

  2023-03-15

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1002/ajmg.a.63180PMID 36919607
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Variability in Phelan-McDermid Syndrome in a Cohort of 210 Individuals

  2022cited by this paper
• Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome

  2021cited by this paper
• Genetic heterogeneity of disorders with overgrowth and intellectual disability: Experience from a center in North India

  2021cited by this paper
• A familial case of overgrowth syndrome caused by a 9q22.3 microdeletion in a mother and daughter.

  2020cited by this paper
• Duplications of GPC3 and GPC4 genes in symptomatic female carriers of Simpson-Golabi-Behmel syndrome type 1.

  2019cited by this paper
• Cantú syndrome: Findings from 74 patients in the International Cantú Syndrome Registry

  2019cited by this paper
• Approach to overgrowth syndromes in the genome era

  2019influential reference
• Rare SUZ12 variants commonly cause an overgrowth phenotype

  2019cited by this paper
• PRC2‐complex related dysfunction in overgrowth syndromes: A review of EZH2, EED, and SUZ12 and their syndromic phenotypes

  2019cited by this paper
• The phenotype of Sotos syndrome in adulthood: A review of 44 individuals

  2019influential reference
• Aberrant Function of the C-Terminal Tail of HIST1H1E Accelerates Cellular Senescence and Causes Premature Aging.

  2019cited by this paper
• Germline pathogenic variant in PIK3CA leading to symmetrical overgrowth with marked macrocephaly and mild global developmental delay

  2019cited by this paper
• Pathogenic Variants in GPC4 Cause Keipert Syndrome.

  2019cited by this paper
• Overgrowth syndromes — clinical and molecular aspects and tumour risk

  2019cited by this paper
• Bi-allelic TMEM94 Truncating Variants Are Associated with Neurodevelopmental Delay, Congenital Heart Defects, and Distinct Facial Dysmorphism.

  2018influential reference
• Novel SUZ12 mutations in Weaver‐like syndrome

  2018influential reference
• Growth pattern of Rahman syndrome

  2018cited by this paper
• A Clinical Review of Generalized Overgrowth Syndromes in the Era of Massively Parallel Sequencing

  2018cited by this paper
• Mutations in Epigenetic Regulation Genes Are a Major Cause of Overgrowth with Intellectual Disability

  2017influential reference
• Mutations in genes encoding polycomb repressive complex 2 subunits cause Weaver syndrome

  2017influential reference
• Homozygous FIBP nonsense variant responsible of syndromic overgrowth, with overgrowth, macrocephaly, retinal coloboma and learning disabilities

  2016cited by this paper
• A recessive syndrome of intellectual disability, moderate overgrowth, and renal dysplasia predisposing to Wilms tumor is caused by a mutation in FIBP gene

  2016influential reference
• Overgrowth Syndromes

  2015cited by this paper
• Neuroimaging and clinical characterization of Sotos syndrome.

  2015cited by this paper
• KBG Syndrome: A Case Report and Longitudinal Assessment of Long‐Acting Recombinant Human Growth Hormone Therapy

  2015cited by this paper
• Proteomic Analysis of the Human Cyclin-dependent Kinase Family Reveals a Novel CDK5 Complex Involved in Cell Growth and Migration*

  2014cited by this paper
• Molecular Mechanisms of Childhood Overgrowth

  2013cited by this paper
• Clinical application of 2.7M Cytogenetics array for CNV detection in subjects with idiopathic autism and/or intellectual disability

  2013cited by this paper
• Overgrowth syndromes

  2012cited by this paper
• SOTOS SYNDROME

  2012influential reference
• Microdeletion 9q22.3 syndrome includes metopic craniosynostosis, hydrocephalus, macrosomia, and developmental delay

  2012cited by this paper
• De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes

  2012cited by this paper
• Array-based comparative genomic hybridization identifies a high frequency of copy number variations in patients with syndromic overgrowth

  2010cited by this paper
• A Microdeletion at 12q24.31 Can Mimic Beckwith-Wiedemann Syndrome Neonatally

  2010influential reference
• Novel duplication in glypican‐4 as an apparent cause of Simpson–Golabi–Behmel syndrome

  2010cited by this paper
• Heterogeneity of NSD1 alterations in 116 patients with Sotos syndrome

  2007cited by this paper
• Genotype-phenotype associations in Sotos syndrome: an analysis of 266 individuals with NSD1 aberrations.

  2005cited by this paper
• Clinical and molecular overlap in overgrowth syndromes

  2005influential reference
• Spectrum of NSD1 gene mutations in southern Chinese patients with Sotos syndrome.

  2005influential reference
• Genotype-Phenotype Correlation in Patients Suspected of Having Sotos Syndrome

  2004influential reference
• GPC4, the gene for human K-glypican, flanks GPC3 on xq26: deletion of the GPC3-GPC4 gene cluster in one family with Simpson-Golabi-Behmel syndrome.

  1998cited by this paper
• Sotos syndrome: evolution of facial phenotype subjective and objective assessment.

  1996cited by this paper

• Coupling deep phenotypic quantification with next-generation phenotyping for 192 individuals with germline histonopathies

  2025cites this paper
• Structural analysis of full-length human transmembrane protein 94 argues against its classification as a P-type Mg2+ ATPase

  2025cites this paper
• Dominant-negative effects of Weaver syndrome-associated EZH2 variants

  2025cites this paper
• Respiratory Involvement in HIST1H1E‐Related Rahman Syndrome: A Case of Severe Mixed Apnea

  2025cites this paper